First CRISPR babies: 6 questions left

The meeting in which He Jiankui said his extraordinary statement that he had helped birth the first babies ̵

1; twin girls – born with edited genomes ended with a statement that worked hard the scientist.

"We have heard an unexpected and profoundly disturbing claim that human embryos have been processed and implanted, resulting in pregnancy and the birth of twins," the statement released by the Organizing Committee of the Second International Human Summit on Genome Edition on November 29 in Hong Kong. "Even if the modifications were reviewed, the procedure was irresponsible and did not conform to international standards."

A similar critique has rained since the revelation earlier this week that he had used the CRISPR-Cas9 to modify the CCR5 gene in two embryos. The gene encoded a protein that many HIV strains use to infect immune cells use in two embryos, which he then implanted in a woman.

As the researchers make an inventory of the week's events, Nature sums up six major questions that are still unanswered.

. 1 Is he in trouble?

On November 27, China's National Ministry of Health called on the Guangdong government to locate its university in the south. The University of Science and Technology should investigate-two days later, the Science Ministry ordered him to stop doing science He had already said that the experiments had been put on hold, as the investigation of Guangdong will go on is not clear. He is accused of violating a directive of the Ministry of Health in 2003, which is not a law and does not contain clear sanctions.

Whether he will do something about him at the University, the Southern University of Science and Technology, is also unclear. A university spokesman said Nature that he "can not disclose such information at this time" and wait for official statements "at a reasonable time". He has been on leave since February 2018, and this is expected to continue until February 2007, January 2021; This week the university criticized his claims and distanced himself from his work.

On November 27, the university-hosted lab website – which he referred to people for information about the genetically-engineered babies – went down, though this was another location for He's Laboratory. Several statements praising He Jiankui's achievements have also disappeared from government agencies. A post on the Science Ministry's website describing a genomic sequencing technology he developed, and a post praising the genomic sequencing technology on the Thousand Talents Plan website – a prestigious program to bring leading academics back to China – both are not accessible now. It is not clear if these actions are related to the events of the week, but both positions were still accessible until recently.

He returned to Shenzhen, where he lives after his lecture at the summit, according to a statement by He's spokesman. Ryan Ferrell and missed on November 29 a scheduled appearance at the summit. "I have returned to Shenzhen and will not be attending the conference on Thursday, and I will stay in China, my home country, and fully cooperate with all inquiries about my work," said the statement.

. 2 Does he agree with the allegations?

Many scientists have said that an independent institution should confirm Er's scientific assertion through a thorough comparison of parents' and children's genes. The problem is, most people agree that babies and their parents should stay anonymous. [19659006] "He has kept them secret for good reasons," says Nobel Prize-winning biologist David Baltimore, chairman of the Summit Organizing Committee and former president of the California Institute of Technology in Pasadena. "We have not even explained how this independent investigation will happen. "

His team could provide anonymized samples and external scientists could also visit He's lab to analyze the data, saying in a statement released by his spokesman He will invite other researchers to an independent investigation Raw data will be made available for third party review. "

He also says that he has submitted studies on his research into human gene editing in journals for publication, and has informed some scientists that a publication of the institute has been published will end of the year, but has not specified which journal, but even if this were the case, strict Chinese genetic resource laws would prevent the release of gene sequences from parents or children.

3. How exactly did CRISPR process the twins? "Genome"

In the absence of a peer-reviewed publication or a In a pre-press review of He's gene editing, some scientists analyze his talk to try to understand how the twins' genomes were handled-and the possible consequences of these changes.

Gaetan Burgio, a geneticist at the Australia National University in Canberra, who is working on the processing of CRISPR gene, says that the raw sequencing data he presented in his presentation suggest that the cells of the babies Several Edi contain versions of the CCR5 gene with different sized DNA deletions. Such a "mosaicism" can be caused when CRISPR processes some early embryo cells differently than others or does not process some. Other researchers reported mosaicism in attempts to process human embryos for research purposes.

Researcher Sean Ryder of the University of Massachusetts Medical School in Worcester Mentioned Other Concerns in a Twitter Post He Jiankui told the Gene Editing Conference that he had targeted the CCR5 gene because some people naturally have a mutation in CCR5 – a deletion of 32-DNA letters known as delta-32 that inactivates the gene. Ryder says, however, that the CCR5 deletions he allegedly introduced into the baby's cells by CRISPR gene editing are not identical to the delta-32 mutation. "The point is that none of the three matches the well-studied delta-32 mutation. As far as I can tell, none has been studied in animal models. Careless, "Ryder wrote in his post.

He Jiankui claims to have given birth to the first babies with altered genomes. Credit: TPG via Zuma

4. When will there be another gene-processed person?

When Jennifer Doudna, a pioneer of the CRISPR / Cas-9 Gene Genesis Gene, heard how he presented his work on November 28th in the summer, she kept coming up with an idea. "The idea I always had was the potential for rogue scientists to use it in an unethical way. It's a real risk, "says Doudna, a biochemist at the University of California, Berkeley,

. Before his revelations, many scientists were already worried that someone was about to create a gened person. Biologist George Daley, Dean of Harvard Medical School, Boston, Massachusetts, and a member of the organizing committee for the summit, pointed to a process in which diseased mitochondrial DNA in one embryo is replaced by another person's healthy mitochondrial DNA, thereby reducing the original disease-causing embryo disease is eliminated mutation. Although mitochondrial replacement therapy does not have the approval of the biomedical community or the US Food and Drug Administration (FDA), physicians from New York City used a baby in Mexico in 2016. "Similar premature practice of embryo processing by CRISPR / Cas9 is likely despite our call for caution," Daley said.

At the Hong Kong Summit, scientists discussed whether another announcement of human germline editing – the change of Genes to pass on to future generations – there is reason to be concerned, "said Baltimore," If someone working in this field gets any indication that this is happening, it is important that the authorities be notified . "

5. Will Ers revelations interfere with ethical efforts to work on the germ line?

Many researchers fear that the disclosure could hamper the future of railroad trackers:" In the US, beats some hedonistic offenses before contradicting the goals of science, "says Baltimore

Following the revelations, FDA Commissioner Scott Gottlieb commented raised concerns for the scientists. "Governments must respond now," he told the news site Biocentury. On November 28, director of the US National Institutes of Health (NIH), Francis Collins, said in a statement that "the need for a binding international consensus on setting limits for this type of research, which is currently being discussed in Hong Kong is never given more obvious. "

The statement made at the Summit summit pleads for clearing a path for the safe implementation of gene editing technology in treatments:" Germline genome editing could become acceptable in the future if these risks are addressed. "

But the debacle has put the germline's interest in gene manipulation, and the fears of a deterrent effect may be exaggerated:" There may be some women excited about the opportunity to participate in this research, " Judith Dar from the University of California's Irvine School of Medicine and the School of Law at a satellite summit meeting asked whether the controversy could deter women from donating eggs for research in the future. nct means to say that this is a debacle but I'm always amazed at the variety of reactions, "she added.

. 6 How will the scientists in future ensure a better overview of the processing of the germline?

"We have no draft, but we have asked academies," Baltimore said. This is a challenge for the world. "

The statement issued by the organizing committee of the summit suggests that science academies around the world should make recommendations to and coordinate with their own governments.

It is also proposed to establish an international forum on research and clinical trials through an international registry and discussing issues such as equitable access to the benefits of gene manipulation, however, genome processing in human embryos may have an unwieldy range of users that could make it difficult to sustain such an organization. "Practical Any laboratory that performs molecular biology uses this technique, "said Daley.

The committee also suggested the need for a" translator "onal pathway, which offers researchers a rigorous and responsible approach to gene-processing the germline into the germ line Klini k to bring. Organizing Committee member Alta Charo, a bioethicist at the University of Wisconsin-Madison, said the expectations must be realistic. "You can not expect perfection. You can try to minimize these incidents by enforcement measures that punish rogue behavior.